Experiments will be performed on four preparations to gain a better understanding of the widespread phenomenon of excitability, which is a property of nerve, muscle, heart, endocrine, and other cells. The Na and K channels of never membrane will be examined in internally perfused, voltage clamped squid giant axons. The basic techniques will be measurement of ionic current, gating current, current fluctuations, and single channel currents. One objective is to devise a kinetic model that harmonizes information derived form all of these techniques. In addition, chemical probes which interact with the channels or their gating machinery will be used, including a variety of drugs, dyes, and mono and divalent cations. The effect of temperature will be examined, with particular attention to a dramatic change in Na channel properties that occurs at low temperature. The electrical properties of cerebral cortical pyramidal cells will be examined in vitro using the brain slice technique. Among our goals are a direct measurement of the space constant of apical dendrites, determination of the excitability properties of soma and dendrites, and characterization of the permeabilities responsible for excitability. The suitability of the first order giant cell in the squid as a physiological preparation will be ascertained. This preparation should be advantageous for the study of soma and denditic properties, and may be useful as a synaptic preparation. The electrical properties of the parathyroid gland will be investigated, with the major objectives of characterizing its electrical activity if any, relating this activity to secretion, and determining the mechanism by which changes of the serum calcium concentration are transduced into electrical activity.